This work describes the distribution of glutamic acid decarboxylase (GAD), a GABA synthesizing enzyme, in the brain. Evidence is also presented which suggests that the stria medullaris (SM), a major fiber system which connects fore- and hindbrain, contains GABAergic afferents to the lateral habenula (LHb). Following SM lesions, it was found that in the LHb GAD activity was decreased by 57% and the uptake of GABA by synaptosomes was reduced by 62%. The medial habenula (MHb) was not affected. The LHb and MHb manifest a differential uptake capacity for GABA and glutamate, showing a higher accumulation by LHb. GABA uptake is predominantly by synaptosomes compared to glial uptake, as shown by drug studies. Part of the GABAergic projection to the LHb appears to originate from the globus pallidus and interpeduncular nuclei. BIBLIOGRAPHIC REFERENCES: Gottesfeld, Z. and Jacobowitz, D.M.: Neurochemical and anatomical studies of GABAergic neurons, Chapter 8 in "Interactions Amongst Putative Neurotransmitters". Raven Press, Pub. (in press), 1977. Gottesfeld, Z., Massari, V.J., Muth, E. A., and Jacobowitz, D.M.: A possible pathway containing GABAergic afferents to the lateral habenula. Brain Res. (in press), 1977.